Effect of diet on brain metabolites and behavior in spontaneously hypertensive rats

Abstract

Attention–deficit hyperactivity disorder (ADHD) is a heterogeneous psychiatric disorder affecting 5-10% of children. One of the suggested mechanisms underlying the pathophysiology of ADHD is insufficient energy supply to neurons. Here, we investigated the role of omega 3 fatty acids in altering neural energy metabolism and behavior of spontaneously hypertensive rats (SHR), which is an animal model of ADHD. To this end, we employed Proton Magnetic Resonance Spectroscopy (1H MRS) to evaluate changes in brain neurochemistry in the SHR following consumption of one of three experimental diets (starting PND 21): Fish Oil Enriched (FOE), Regular (RD) and Animal Fat Enriched (AFE) diet. Behavioral tests were performed to evaluate differences in locomotor activity and risk-taking behavior (starting PND 44). Comparison of frontal lobe metabolites showed that increased amounts of omega 3 fatty acids decreased total Creatine levels (tCr), but did not change glutamate (Glu), total N-acetylaspartate (tNAA), Lactate (Lac), Choline (Cho) or Inositol (Ino) levels. Although behavior was not significantly affected by different diets, significant correlations were observed between brain metabolites and behavior in the open field and elevated plus maze. SHR with higher levels of brain tCr and Glu exhibited greater hyperactivity in a familiar environment. On the other hand, risk-taking exploration of the elevated plus maze's open arms correlated negatively with forebrain tNAA and Lac levels. These findings support the possible alteration in energy metabolites in ADHD, correlating with hyperactivity in the animal model. The data also suggest that omega 3 fatty acids alter brain energy and phospholipid metabolism.

High‐fat diet induces a neurometabolic state characterized by changes in glutamate and N‐acetylaspartate pools associated with early glucose intolerance: An in vivo multimodal MRI study

“…Also, our observed neurochemical alterations begin before the establishment of hyperglycemia, which possibly would later on shift neurometabolic profiles in case of uncontrolled hyperglycemia, as suggested by the mentioned studies and our own results. Finally, it should be noted that the composition of the dietary regimens varies across studies (consisting in distinct amounts of triglycerides and carbohydrates) which represents another factor influencing distinct metabolic profiles in high‐fat diet stats . All these notions might, therefore, provide an explanatory framework for the distinct hippocampal results found across different studies focusing on disparate metabolic stages and even animal models.…”

“…Besides causing long‐term dysfunction of several organs, T2DM has been shown to affect also the central nervous system leading to dysregulation in neurotransmission, cognitive impairment and even dementia . It has been suggested that such features may start to develop in unhealthy obesity and prediabetes scenarios with recent studies supporting the earlier development of metabolic dysregulation being associated to subclinical insulin resistance, adipose tissue dysfunction, inflammation, and oxidative stress . Although the underlying mechanisms are not fully understood, it has been reported that they may emerge from metabolic perturbations at multiple levels, also affecting brain integrity, particularly the hippocampus …”

“…Regardless of the extensive research, findings of neurotransmission, metabolic and structural alterations in obesity and prediabetes‐like conditions (high‐fat diet induced), remain largely unexplored and to some extent contradictory. So far, there are only a few studies which assessed such parameters in those conditions and, to the best of our knowledge, fewer have addressed concomitant structural changes by means of high‐field MRI . For instance, in an 1 H‐MRS experiment involving mice submitted to a high‐caloric diet, reductions in several metabolite levels, particularly glutamate and N‐acetylaspartate were reported in the absence of other changes such as in inflammation markers(18).…”

Diurnal variability of cerebral metabolites in healthy human brain with 2D localized correlation spectroscopy (2D L‐COSY)

“…We did not account for any gender effects during analysis. Despite previous animal studies showing an omega‐3 fatty acid‐rich diet can alter brain metabolites and phospholipids, but not hydration, we did not control our subjects for hydration, diet, or sleep in our study. This is not surprising, as most clinical MRS sequences are performed at the end of the standard structural protocol, which does not require participants to follow any dietary restrictions or sleep patterns and controlling these just for MRS is nearly impossible and quite impractical.…”

Dietary long-chain omega-3 fatty acids are related to impulse control and anterior cingulate function in adolescents

“…Interestingly, omega-3 deficiency has been shown to impair cortical glucose transport and utilization (Pifferi et al, 2005;Ximenes da Silva et al, 2002) and boys with lower omega-3 status exhibit indices of metabolic dysfunction in the ACC compared to their higher omega-3 peers (McNamara et al, 2013). Furthermore, omega-3 supplementation resulted in increased frontocortical efficiency in a rodent ADHD model (Liso Navarro et al, 2014).…”